Zhu Fang, Zi Liu, Yang Peng, Wei Yang, Zhong Rui, Wang Yan, You Chao, Li Yiwen, Tian Meng, Gu Zhipeng
College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials Engineering, Sichuan University, Chengdu, Sichuan 610065, P. R. China.
Neurosurgery Research Laboratory, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China.
ACS Appl Mater Interfaces. 2021 Mar 3;13(8):9729-9738. doi: 10.1021/acsami.1c00491. Epub 2021 Feb 18.
Intracerebral hemorrhage (ICH) will be accompanied by the overload of iron and reactive oxygen species (ROS) following hematoma clearance. Although deferoxamine (DFO) has been widely utilized as a clinical first-line siderophore to remove the iron overload, the ROS-inducing damage still greatly limits the therapeutic effect of DFO. To address this issue, we designed and fabricated a series of dual-functional macromolecular nanoscavengers featuring high-density DFO units and catechol moieties. Note that the former units could effectively remove the iron overload, while the latter ones could efficiently deplete the ROS. The resulting nanoscavengers efficiently down-regulate the iron and ROS levels as well as significantly reduce the cell death in both iron-overloaded RAW 264.7 cells and the ICH mice model. This work suggests a novel clue for the ICH-ameliorated iron-depleting interventional therapeutic regimen.
脑出血（ICH）在血肿清除后会伴随着铁和活性氧（ROS）的过载。尽管去铁胺（DFO）已被广泛用作临床一线铁载体以去除铁过载，但ROS诱导的损伤仍然极大地限制了DFO的治疗效果。为了解决这个问题，我们设计并制备了一系列具有高密度DFO单元和儿茶酚部分的双功能大分子纳米清除剂。请注意，前者可以有效去除铁过载，而后者可以有效消耗ROS。所得的纳米清除剂有效下调铁和ROS水平，并显著减少铁过载的RAW 264.7细胞和ICH小鼠模型中的细胞死亡。这项工作为改善ICH的铁消耗介入治疗方案提供了新的线索。
